4HFR

Human 11beta-Hydroxysteroid Dehydrogenase Type 1 in complex with an orally bioavailable acidic inhibitor AZD4017.

4HFR の概要

• エントリーDOI: 10.2210/pdb4hfr/pdb
• 分子名称: Corticosteroid 11-beta-dehydrogenase isozyme 1, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, {(3S)-1-[5-(cyclohexylcarbamoyl)-6-(propylsulfanyl)pyridin-2-yl]piperidin-3-yl}acetic acid, ... (4 entities in total)
• 機能のキーワード: alpha beta, rossmann fold, nadp, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane ; Single-pass type II membrane protein : P28845
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62075.10

構造登録者

Ogg, D.J.,Gerhardt, S.,Hargreaves, D. (登録日: 2012-10-05, 公開日: 2012-10-17, 最終更新日: 2023-09-20)

主引用文献

Scott, J.S.,Bowker, S.S.,Deschoolmeester, J.,Gerhardt, S.,Hargreaves, D.,Kilgour, E.,Lloyd, A.,Mayers, R.M.,McCoull, W.,Newcombe, N.J.,Ogg, D.,Packer, M.J.,Rees, A.,Revill, J.,Schofield, P.,Selmi, N.,Swales, J.G.,Whittamore, P.R.
Discovery of a Potent, Selective, and Orally Bioavailable Acidic 11 -Hydroxysteroid Dehydrogenase Type 1 (11 -HSD1) Inhibitor: Discovery of 2-[(3S)-1-[5-(Cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic Acid (AZD4017)
J.Med.Chem., 55:5951-5964, 2012

PubMed Abstract: Inhibition of 11β-HSD1 is an attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. We report here the discovery of a nicotinic amide derived carboxylic acid class of inhibitors that has good potency, selectivity, and pharmacokinetic characteristics. Compound 11i (AZD4017) is an effective inhibitor of 11β-HSD1 in human adipocytes and exhibits good druglike properties and as a consequence was selected for clinical development.

PubMed: 22691057
DOI: 10.1021/jm300592r

実験手法

X-RAY DIFFRACTION (2.73 Å)